title: SHIP2 signaling in normal and pathological situations: Its impact on cell proliferation.
abstract: Phosphoinositide 5-phosphatases are critical enzymes in modulating the concentrations of PI(3,4,5)P3, PI(4,5)P2 and PI(3,5)P2. The SH2 domain containing inositol 5-phosphatases SHIP1 and SHIP2 belong to this family of enzymes that dephosphorylate the 5 position of PI(3,4,5)P3 to produce PI(3,4)P2. Data obtained in zebrafish and in mice have shown that SHIP2 is critical in development and growth. Exome sequencing identifies mutations in the coding region of SHIP2 as a cause of opsismodysplasia, a severe but rare chondrodysplasia in human. SHIP2 has been reported to have both protumorigenic and tumor suppressor function in human cancer very much depending on the cell model. This could be linked to the relative importance of PI(3,4)P2 (a product of SHIP2 phosphatase activity) which is also controlled by the PI 4-phosphatase and tumor suppressor INPP4B. In the glioblastoma cell line 1321 N1, that do not express PTEN, lowering SHIP2 expression has an impact on the levels of PI(3,4,5)P3, cell morphology and cell proliferation. It positively stimulates cell proliferation by decreasing the expression of key regulatory proteins of the cell cycle such as p27. Together the data point out to a role of SHIP2 in development in normal cells and at least in cell proliferation in some cancer derived cells.
authors.affiliation: Interdisciplinary Research Institute (IRIBHM), Université Libre de Bruxelles, Campus Erasme, Bldg C, 808 Route de Lennik, 1070 Brussels, Belgium.
authors.forename: William's
authors.initials: W
authors.lastname: Elong Edimo
authors.affiliation: Laboratoire de Génétique fonctionnelle, GIGA-Research Centre, Secteur de Biochimie Métabolique, Département des Sciences Fonctionnelles (Faculté de Médecine vétérinaire), Université de Liège, 1 rue de l'Hôpital, 4000 Liège, Belgium; Walloon Excellence in Lifesciences and Biotechnology (WELBIO), Belgium.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Schurmans
authors.affiliation: Interdisciplinary Research Institute (IRIBHM), Université Libre de Bruxelles, Campus Erasme, Bldg C, 808 Route de Lennik, 1070 Brussels, Belgium; Walloon Excellence in Lifesciences and Biotechnology (WELBIO), Belgium.
authors.forename: Pierre P
authors.initials: PP
authors.lastname: Roger
authors.affiliation: Interdisciplinary Research Institute (IRIBHM), Université Libre de Bruxelles, Campus Erasme, Bldg C, 808 Route de Lennik, 1070 Brussels, Belgium. Electronic address: cerneux@ulb.ac.be.
authors.forename: Christophe
authors.initials: C
authors.lastname: Erneux
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D010716:Phosphatidylinositols / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D010716:Phosphatidylinositols; D010744:Phosphoric Monoester Hydrolases